We propose to define the relationships between membrane permeability, cation content, cation transport and energy production in resting and lectin-stimulated normal T and B and leukemic lymphocytes. First, the intrinsic lymphocyte membrane permeability to potassium will be determined by defining the rate constants for potassium efflux and influx using K42. Plant lectin-induced alterations of potassium permeability will then be quantitated. Parallel experiments will be performed to define true active potassium transport by human lymphocytes. This transport represents only a part of the isotopic potassium influx and is measured by net cellular potassium fall when transport is blocked. These studies will demonstrate whether lectin-stimulation results in an increase in transport against a gradient or simply an increase in K ion minus K ion exchange. Since concentrative transport requires the expenditure of energy, the individual contributions of glycolysis and tricarboxylic acid cycle activity to transport will be measured. Thus, the component of increased metabolic activity devoted to transport after lectin treatment will be determined. Because we have shown that lectins alter the ability of the lymphocyte membrane to contain molecules the size of amino acids, we will also examine alterations in plasma membrane permeability to larger molecules such as nucleotides and cyclic nucleotides. We will define, likewise, the potassium permeability, transport and metabolic activity in leukemic lymphocytes (CLL) and lymphoblasts (ALL) and their responses to lectin and non-lectin mitogens. These studies should contribute to the understanding of: a) lymphocyte membrane permeability and transport, b) the response in strict quantitative terms of these membrane functions to mitogens, c) the linkage of cell metabolism to membrane transport, and d) the possible alterations of these interrelated processes in leukemic cells. BIBLIOGRAPHIC REFERENCES: Segel, G.B., Gordon, B.R., Lichtman, M.A., Hollander, M.M., Klemperer, M.R. Exodus of K-42 and Rb-86 from rat thymic and human blood lymphocytes exposed to phyto-hemagglutinin. J. Cell. Physiol., 87:337, 1976.